# Design, Synthesis and Biological Evaluation of Novel Furanocoumarin Derivatives: Validation of Anti-Osteoporotic Efficacy In Vitro and In Vivo

## TL;DR

Researchers designed and tested new furanocoumarin compounds to treat osteoporosis, finding one, B15, to be less toxic and more effective than a natural compound.

## Contribution

A novel furanocoumarin derivative, B15, with reduced toxicity and improved anti-osteoporotic efficacy is developed and validated.

## Key findings

- Compound B15 showed less toxicity and better inhibition of osteoclast formation compared to ISO in vitro.
- B15 decelerated osteoporosis progression in ovariectomized mice by improving bone microarchitecture and serum markers.
- B15 significantly increased estradiol levels in ovariectomized mice, suggesting a hormonal mechanism.

## Abstract

Background/Objectives: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture. It has become a major clinical challenge due to the limitations of current therapeutic approaches. Isoimperatorin (ISO), a naturally occurring and biologically active furanocoumarin extracted from various traditional herbals, exhibits therapeutic potential in combating osteoporosis. However, toxicity limits its application. Methods: In vivo, compound B15 was evaluated in an Ovariectomy (OVX) mice model, where treatment was associated with changes in bone microarchitecture parameters, modulation of serum bone metabolism markers, and alterations in the histopathological features of bone tissue. Results: In this study, a new series of furanocoumarin derivatives was designed and synthesized for the treatment of osteoporosis. Compared with ISO, compound B15 has less toxicity and better ability to inhibit osteoclast formation in vitro. Compound B15 could decelerate the progression of osteoporosis in ovariectomized mice. It is worth mentioning that the expression of estradiol in the serum of mice with excised ovaries was significantly increased by compound B15. Conclusions: These results imply that the novel furanocoumarin derivative B15 is a promising therapeutic option for osteoporosis.